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Cytomegalovirus infection as an underestimated trigger for checkpoint inhibitor-related pneumonitis in lung cancer: a retrospective study

Clinical and Translational Oncology Aims and scope Submit manuscript

Abstract

Objectives

Checkpoint inhibitor-related pneumonitis (CIP) is a rare but potentially fatal complication of immune checkpoint inhibitors (ICIs). At present, the mechanism of CIP is not completely clear. Cytomegalovirus (CMV) infection is widespread in the population. Chemotherapy and radiotherapy can lead to the reactivation of CMV. We aimed to investigate the association between CMV infection and CIP.

Materials and methods

We retrospectively identified all lung cancer patients treated with ICIs at our institute from January 2016 to May 2020. The association between the development of CIP and CMV infection status was analyzed.

Results

Among 251 cases analyzed, 29 (11.6%) patients with CIP were identified, of whom 12 (4.78%) cases had grade 3–4 CIP. All 12 patients with grade 3–4 pneumonitis were CMV-IgG-positive, indicating a previous CMV infection. Except for one CMV-DNA-positive patient, the other patients were CMV-DNA-negative. All but one patient was CMV pp65 antigen-positive, indicating an early reactivation of the virus. The histological features of CMV pneumonia were not found in all available lung tissues, including lung transplantation pathology in one patient and lung biopsies in three patients. Except for one patient who received delayed antiviral therapy, the symptoms improved after glucocorticoid combined with antiviral therapy.

Conclusions

The use of ICIs can restore the immune function and cause an immune response to CMV antigen while the infection is still latent. Our study suggests that CIP may be an immune reconstitution syndrome associated with CMV infection. CMV infection may represent a potentially important trigger for CIP. Patients with severe CIP should be vigilant against CMV infection. The early use of glucocorticoid combined with antiviral therapy is pivotal to good prognosis.

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Acknowledgements

Not applicable.

Funding

This work was supported by the Special Fund Project of Science and Technology in Guangdong Province (2017B020247038, to X. Lin),State Key Laboratory of Respiratory Disease-The Independent project (SKLRD-QN-201720, to C. Zhou), State Key Laboratory of Respiratory Disease-The open project (SKLRD-OP-2018011, to C. Zhou), Guangdong High Level University Clinical Cultivation Project (2018–2022) (to C. Zhou) and Xinjiang Kashgar Science and Technology Project (KS2017006, to X. Lin).

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Author notes

  1. Xinqing Lin, Tingting Lu and Shiyue Li contributed equally to this work.

Authors and Affiliations

  1. Department of Respiratory and Critical Medicine, Jinling Hospital, Nanjing Clinical School of Southern Medical University, 305# East Zhongshan Road, Guangzhou, Nanjing, 210002, China

    X. Lin & Y. Song

  2. State Key Laboratory of Respiratory Disease, National Clinical Research Centre for Respiratory Disease, Guangzhou Institute of Respiratory Health, First Affiliated Hospital, Guangzhou Medical University, 151# Yanjiang Road, Guangzhou, 510120, China

    X. Lin, S. Li, X. Xie, X. Chen, J. Jiang, Y. Qin, Z. Xie, M. Liu, M. Ouyang, N. Zhong & C. Zhou

  3. Department of Neurology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China

    T. Lu

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Contributions

XL, NZ, YS and CZ contributed to the study concept and design. YS and CZ had full access to all the data and took responsibility for the integrity of the data and the accuracy of the data analysis. XL, XC, JJ, YQ and ZX collected the data. XL and TL contributed to the analysis and interpretation of the data. XL and TL draft the manuscript. ML and MO helped interpret the data and draft the manuscript. All authors contributed to the revisions of and approved the final manuscript.

Corresponding authors

Correspondence to Y. Song or C. Zhou.

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Conflict of interest

The authors declare that they have no conflict of interests.

Ethics approval and consent to participate

This study was approved by the local Ethics Committee of the First Affiliated Hospital of Guangzhou Medical University.

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Lin, X., Lu, T., Li, S. et al. Cytomegalovirus infection as an underestimated trigger for checkpoint inhibitor-related pneumonitis in lung cancer: a retrospective study. Clin Transl Oncol 23, 389–396 (2021). https://doi.org/10.1007/s12094-020-02432-5

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  • DOI: https://doi.org/10.1007/s12094-020-02432-5

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